Mitochondrion-toxic drugs given to patients with mitochondrial psychoses

Abstract

Commentary The cause and pathophysiology of mood and psychotic disorders, including unipolar depression, bipolar disorder, and schizophrenia, is variable. Several scenarios have been proposed to explain the development of psychoses, one of which is mitochondrial dysfunction (mitochondrial mood and psychotic disorders) [1,2]. Impaired mitochondrial pathways, which may be associated with mood and psychotic disorders, include the respiratory chain (Figure 1) [1,3], the pyruvate-dehydrogenase complex, the 2-ketoglutarate dehydrogenase [4], and the polyol pathway [5]. Disturbance of the respiratory chain is the most frequent cause of mitochondrial mood and psychotic disorders. Mood and psychotic disorders in patients with mitochondrial disorders may be the sole manifestation, or one among other manifestations, of a mitochondrial disorder. Mood and psychotic disorders may be the dominant feature of the phenotype or a collateral finding, and may occur in syndromic as well as non-syndromic [5,6] mitochondrial disorders. A recent study, published in this journal [1], aimed to assess psychiatric abnormalities in mitochondrial disorders with a proven mtDNA defect [1]. Twelve patients had a syndromic mitochondrial disorder (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), myoclonic epilepsy with ragged red fibers (MERRF), neuropathy, ataxia, and retinitis pigmentosa (NARP), progressive external ophthalmoplegia (PEO), Kearns-Sayre syndrome (KSS)) and seven patients had a non-syndromic mitochondrial disorder. The frequency of psychiatric diagnoses among these patients was reported to be 47% [1]. Psychiatric conditions may be even more common in other studies and include major depression, agoraphobia and/or panic disorder, generalized anxiety disorder, social anxiety disorder, or psychotic syndromes [7]. The medication these patients took at inclusion was provided for only nine patients. Among these drugs, however, several are reported to be mitochondriontoxic. Two patients were medicated with valproic acid, two